Grant: Team Grant: Preparation to Trial: Inflammation for Chronic Conditions

Exercise holds potential to reduce inflammation and slow brain aging; however, these effects are highly variable in people with age related inflammatory comorbidities like cardiovascular disease or diabetes. With aging, we have identified changes in the way the body processes good fats from diet, limiting their anti-inflammatory benefits. This is due to an enzyme, soluble epoxide hydrolase (sEH), that breaks down good fats. Excess sEH renders fat metabolism less effective at controlling inflammation. Normally, this enzyme pathway is involved in the body's response to exercise, but in older people with chronic low-grade inflammation, it might become a problem. We will follow people with diabetes or heart disease over 6 months of exercise and measure sEH metabolites in their blood before beginning and after 3 and 6 months. We hypothesize that people who have more sEH metabolites in their blood will have smaller cognitive benefits of exercise over time. Furthermore, we hypothesize that sEH metabolites will be related to damage of the brain's smallest blood vessels, their ability to regulate blood flow, and less blood supply to the brain and peripheral tissues. If this is true, the benefits of exercise might be optimized for people with heart disease or diabetes in future studies by combining exercise interventions with a drug that blocks sEH to protect the brain's small vessels. This study will determine for which of these populations that drug might be beneficial.